The cellular receptor for urokinase (uPAR, CD87) plays multiple functions in cell migration, cell adhesion, pericellular proteolysis and tissue remodeling. uPAR is expressed by most leukocytes including monocytes, macrophages, neutrophils and platelets. uPAR is an activation antigen in monocytes and T cells and T-cells from HIV-1 infected individuals express elevated levels of uPAR1, 1994. HIV-1 infection of leukocytes in vitro causes up-regulation of uPAR cell surface expression in a process which appear to be coordinated temporally with the onset of viral replication2.
uPAR may be shed from the cell surface generating a soluble form of the receptor (suPAR) lacking the GPI-anchor. The shedding mechanism is poorly understood but may occur by GPI-specific phospholipase D catalyzed hydrolytic cleavage of the GPI-anchor). Soluble forms of uPAR (suPAR) has been identified in cell culture supernatants and in diverse biological fluids such as tumor ascites, cystic fluid, serum, plasma and recently also in urine 3.
Serum, plasma and urine levels of suPAR are elevated in patients suffering from different types of cancer4, the paroxysmal nocturnal hemoglobinuria syndrome (PNH) syndrome5, and in rheumatoid arthritis patients6. The plasma level of suPAR is furthermore a prognostic marker for overall survival in patients suffering from HIV-1 infection7.
The cellular origin of circulating suPAR is not known. Many, if not all, cells which express uPAR also shed soluble forms of the receptor when cultured in vitro. The source of excess serum suPAR in cancer patients has been suggested to derive from the cancer cells and/or tumor-infiltrating macrophages as these cells often express high levels of uPAR and experiments using xenografted mice carrying human tumors have indeed demonstrated that the tumor tissue does release suPAR to the circulation and urine8.